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Interactions of Conjugated-Linoleic Acid and Alpha-Lipoic Acid on Insulin Action in the Insulin-resistant Obese Zucker Rat.
Taylor ZC, Teachey MK, Saengsirisuwan V, O’Keefe MP, and Henriksen EJ, Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, AZ
The essential fatty acid conjugated-linoleic acid (CLA) and the antioxidant R-alpha-lipoic acid (R-ALA) individually have been shown to enhance glucose tolerance and insulin action on skeletal muscle glucose transport in insulin-resistant states. However, to date, no study has assessed the potential interactions between these two interventions in treating insulin resistance. Therefore, the purpose of this study was to assess the interactions of low doses of CLA and R-ALA on whole-body insulin sensitivity and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker (fa/fa) rat. Female obese Zucker rats (~7-8 wk old) were treated with either vehicle or submaximal doses of CLA (0.3 g/kg body wt) or R-ALA (10 mg/kg), individually and in combination, for 21 days. The glucose-insulin index, an indirect indicator of whole-body insulin sensitivity derived from an oral glucose tolerance test, was not altered by this dose of R-ALA compared to the vehicle-treated control group. However, CLA alone caused a 17% decrease (p<0.05) in this variable, indicating an enhancement of insulin sensitivity. The greatest improvement in whole-body insulin sensitivity was associated with the combination treatment, as the largest decrease (21%) in the glucose-insulin index was observed. Insulin-mediated (5 mU/ml) glucose transport activity (as assessed by in vitro 2-deoxyglucose uptake) in both the type I soleus and the type IIb epitrochlearis was not altered by treatment with R-ALA. CLA induced a 37% increase in insulin-mediated glucose transport in the epitrochlearis only. Most importantly, the combination of R-ALA and CLA induced the greatest improvements in insulin-mediated glucose transport in both the epitrochlearis (77%) and the soleus (54%) muscles. These results suggest that R-ALA and CLA treatment in combination improves whole-body insulin sensitivity and insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat to a greater degree than either intervention individually. (Supported by BASF AG, Ludwigshafen, Germany (EJH) and the University of Arizona Undergraduate Biology Research Program (ZCT).)
Interactions of Conjugated-Linoleic Acid and Alpha-Lipoic Acid on Insulin Action in the Insulin-resistant Obese Zucker Rat.
Taylor ZC, Teachey MK, Saengsirisuwan V, O’Keefe MP, and Henriksen EJ, Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine, Tucson, AZ
The essential fatty acid conjugated-linoleic acid (CLA) and the antioxidant R-alpha-lipoic acid (R-ALA) individually have been shown to enhance glucose tolerance and insulin action on skeletal muscle glucose transport in insulin-resistant states. However, to date, no study has assessed the potential interactions between these two interventions in treating insulin resistance. Therefore, the purpose of this study was to assess the interactions of low doses of CLA and R-ALA on whole-body insulin sensitivity and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker (fa/fa) rat. Female obese Zucker rats (~7-8 wk old) were treated with either vehicle or submaximal doses of CLA (0.3 g/kg body wt) or R-ALA (10 mg/kg), individually and in combination, for 21 days. The glucose-insulin index, an indirect indicator of whole-body insulin sensitivity derived from an oral glucose tolerance test, was not altered by this dose of R-ALA compared to the vehicle-treated control group. However, CLA alone caused a 17% decrease (p<0.05) in this variable, indicating an enhancement of insulin sensitivity. The greatest improvement in whole-body insulin sensitivity was associated with the combination treatment, as the largest decrease (21%) in the glucose-insulin index was observed. Insulin-mediated (5 mU/ml) glucose transport activity (as assessed by in vitro 2-deoxyglucose uptake) in both the type I soleus and the type IIb epitrochlearis was not altered by treatment with R-ALA. CLA induced a 37% increase in insulin-mediated glucose transport in the epitrochlearis only. Most importantly, the combination of R-ALA and CLA induced the greatest improvements in insulin-mediated glucose transport in both the epitrochlearis (77%) and the soleus (54%) muscles. These results suggest that R-ALA and CLA treatment in combination improves whole-body insulin sensitivity and insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat to a greater degree than either intervention individually. (Supported by BASF AG, Ludwigshafen, Germany (EJH) and the University of Arizona Undergraduate Biology Research Program (ZCT).)
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